Editorial
Continuous or intermittent? On the dosing schedule of sunitinib for advanced renal cell carcinoma Masahiro Nozawa, Hirotsugu Uemura Department of Urology, Kinki University Faculty of Medicine, Japan Correspondence to: Masahiro Nozawa, MD, PhD. 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan. Email: [email protected]. Submitted Apr 15, 2012. Accepted for publication May 03, 2012. doi: 10.3978/j.issn.2223-4683.2012.05.02 Scan to your mobile device or view this article at: http://www.amepc.org/tau/article/view/636/682
Sunitinib is globally approved for treatment of advanced renal cell carcinoma (RCC) at a dosage of 50 mg/day with four weeks on treatment and two weeks off, based on a randomized phase III trial in which its superiority over interferon alpha was established as first-line therapy for patients with metastatic RCC (1). On the other hand, continuous daily dosing of sunitinib at a dosage of 37.5 mg/day may be expected to provide consistent antitumor activity with a better safety profile compared with the 50 mg/day intermittent schedule according to two phase II trials (2,3). The recently published paper reported the result of a very interesting randomized phase II study called “Renal EFFECT Trial”, in which the efficacy and safety of sunitinib was directly compared between the 50 mg/day intermittent schedule and the continuous 37.5 mg/day as first-line therapy for patients with advanced RCC (4). In this study, patients with treatment-naïve, clear cell advanced RCC were randomly assigned in a 1:1 ratio to receive sunitinib 50 mg/day with four weeks on treatment and two weeks off (schedule 4/2) or 37.5 mg/day on a continuous daily dosing schedule (CDD), with 146 patients in each arm. The primary end point was time to tumor progression (TTP). As a result, although statistically not significant, a longer TTP and progression-free survival (PFS) was observed with the 4/2 schedule. Median TTP in the 4/2 schedule and CDD arms was 9.9 months (95% CI, 7.0 to 13.4 months) and 7.1 months (95% CI, 6.8 to 9.7 months), respectively (hazard ratio [HR], 0.77; 95% CI, 0.57 to 1.04; P=0.090). Median PFS was 8.5 months (95% CI, 6.9 to 11.1 months) and 7.0 months (95% CI, 6.0 to 8.7 months) in the schedule 4/2 and CDD arms, respectively (HR, 0.77; 95% CI, 0.58 to 1.02; P=0.070). No significant difference between the schedule 4/2 and CDD © Translational Andrology and Urology. All rights reserved.
arms was observed in objective response rate (32% and 28%, respectively), stable disease rate (43% and 49%, respectively), or overall survival (median, 23.1 and 23.5 months, respectively). Patient baseline characteristics were similar between both arms, although a slightly higher number of patients had a lower Karnofsky performance status, MSKCC poor risk disease, and liver metastases in the CDD arm compared with the schedule 4/2 arm. When analyzed by the MSKCC risk criteria, however, the relative increase in TTP with the 4/2 schedule was most pronouncedly shown in the favorable-risk (HR, 0.56; 95% CI, 0.29 to 1.07; P=0.075) rather than in the intermediate or poorrisk group. Moreover, in the multivariable analysis which assessed an independent relationship for each variable studied among a range of pretreatment clinical features, the trend for longer TTP (HR, 0.74; 95% CI, 0.53 to 1.01; P=0.061) and PFS (HR, 0.75; 95% CI, 0.55 to 1.02; P=0.071) with schedule 4/2 was observed. Predictors for TTP were baseline lung or bone metastases within the multivariable analysis. What about safety and tolerability? Median treatment duration was five months (range,
Continuous or intermittent? On the dosing schedule of sunitinib for advanced renal cell carcinoma Masahiro Nozawa, Hirotsugu Uemura Department of Urology, Kinki University Faculty of Medicine, Japan Correspondence to: Masahiro Nozawa, MD, PhD. 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan. Email: [email protected]. Submitted Apr 15, 2012. Accepted for publication May 03, 2012. doi: 10.3978/j.issn.2223-4683.2012.05.02 Scan to your mobile device or view this article at: http://www.amepc.org/tau/article/view/636/682
Sunitinib is globally approved for treatment of advanced renal cell carcinoma (RCC) at a dosage of 50 mg/day with four weeks on treatment and two weeks off, based on a randomized phase III trial in which its superiority over interferon alpha was established as first-line therapy for patients with metastatic RCC (1). On the other hand, continuous daily dosing of sunitinib at a dosage of 37.5 mg/day may be expected to provide consistent antitumor activity with a better safety profile compared with the 50 mg/day intermittent schedule according to two phase II trials (2,3). The recently published paper reported the result of a very interesting randomized phase II study called “Renal EFFECT Trial”, in which the efficacy and safety of sunitinib was directly compared between the 50 mg/day intermittent schedule and the continuous 37.5 mg/day as first-line therapy for patients with advanced RCC (4). In this study, patients with treatment-naïve, clear cell advanced RCC were randomly assigned in a 1:1 ratio to receive sunitinib 50 mg/day with four weeks on treatment and two weeks off (schedule 4/2) or 37.5 mg/day on a continuous daily dosing schedule (CDD), with 146 patients in each arm. The primary end point was time to tumor progression (TTP). As a result, although statistically not significant, a longer TTP and progression-free survival (PFS) was observed with the 4/2 schedule. Median TTP in the 4/2 schedule and CDD arms was 9.9 months (95% CI, 7.0 to 13.4 months) and 7.1 months (95% CI, 6.8 to 9.7 months), respectively (hazard ratio [HR], 0.77; 95% CI, 0.57 to 1.04; P=0.090). Median PFS was 8.5 months (95% CI, 6.9 to 11.1 months) and 7.0 months (95% CI, 6.0 to 8.7 months) in the schedule 4/2 and CDD arms, respectively (HR, 0.77; 95% CI, 0.58 to 1.02; P=0.070). No significant difference between the schedule 4/2 and CDD © Translational Andrology and Urology. All rights reserved.
arms was observed in objective response rate (32% and 28%, respectively), stable disease rate (43% and 49%, respectively), or overall survival (median, 23.1 and 23.5 months, respectively). Patient baseline characteristics were similar between both arms, although a slightly higher number of patients had a lower Karnofsky performance status, MSKCC poor risk disease, and liver metastases in the CDD arm compared with the schedule 4/2 arm. When analyzed by the MSKCC risk criteria, however, the relative increase in TTP with the 4/2 schedule was most pronouncedly shown in the favorable-risk (HR, 0.56; 95% CI, 0.29 to 1.07; P=0.075) rather than in the intermediate or poorrisk group. Moreover, in the multivariable analysis which assessed an independent relationship for each variable studied among a range of pretreatment clinical features, the trend for longer TTP (HR, 0.74; 95% CI, 0.53 to 1.01; P=0.061) and PFS (HR, 0.75; 95% CI, 0.55 to 1.02; P=0.071) with schedule 4/2 was observed. Predictors for TTP were baseline lung or bone metastases within the multivariable analysis. What about safety and tolerability? Median treatment duration was five months (range,
